ImAginE

Immunology and Ageing in Europe

Thematic EU Network coordinated by
G. Pawelec

The Scientific objectives are to obtain insights into the basic cellular and molecular mechanisms underlying the decreased proliferative and functional capacity of aged T lymphocytes and to
identify those characteristics which are critical for ageing processes. The ultimate aim is to use this knowledge to examine ways of delaying or preventing T cell senescence in these preclinical
in vitro model systems and to examine the effects of these manipulations on the expression of the identified characteristics paralleling T cell ageing.

The expected achievements of this project are

successful scale-up for the generation of sufficient T cell clones (TCC) for distribution to members and transfer of T cell culture and cloning technology;

the establishment of candidate causative factors for T cell immunosenescence in longitudinal in vitro models of ageing and their validation in multiple laboratories in a quality-control
exercise in vitro; finally, selection of those for testing in vivo;

the validation of these selected candidates on T cells ex vivo from a large range of donors of different ages and in different states of physical and mental health in cross-sectional and
longitudinal studies;

the manipulation of T cell senescence in vitro in the ageing model and assessment of the impact of such manipulations on function and surface phenotypes of the cells for monitoring purposes;

carrying out trials involving proband manipulation, such as dietary supplementation and eventually other senescence-modulating interventions in vivo, and monitoring their T cells for
age-associated changes.

The coordination objectives are

to re-establish a central facility (CF) to collect, produce and bank cells and data pertaining to these, for use by members of ImAginE. This requires re-establishing and modernizing the
web-site (still extant under www.medizin.uni-tuebingen/eucambis/) as well as the physical and virtual cell and data banks;

to generate sufficient in vitro cultured T cell clones for distribution to selected members for study in the first phase of the project. These must be expanded to large numbers and
cryopreserved [using the EUCAMBIS equipment]. Each batch must be pre-checked for viability and sterility before shipping on dry ice to members;

to collect and integrate data from members obtained using these centrally-distributed materials for comparison and quality control at the CF;

to facilitate communication between relevant groups by establishing an interactive web site for display of the latest central data analyses from the ImAginE studies;

to agree on the characteristics to be studied in the second phase of the project, ie. screening on the unique donor material available to the various members;

to collect and integrate these data at the central facility;

to coordinate attempts to develop methods for extending the lifespan of T cells in vitro;

to assess whether such interventions may be possible in vivo;

to organise meetings and short-term personnel exchange to facilitate the performance of the project.